TY - JOUR
T1 - Engineered 3D hydrogels with full-length fibronectin that sequester and present growth factors
AU - Trujillo, Sara
AU - Gonzalez-Garcia, Cristina
AU - Rico, Patricia
AU - Reid, Andrew
AU - Windmill, James
AU - Dalby, Matthew J.
AU - Salmeron-Sanchez, Manuel
N1 - Funding Information:
Longitudinal sections of the paraffin embedded forearms were stained with safranin-O (that stains for cartilage, in red), fast green (that stains for collagen) and haematoxylin (to counterstain the nuclei) ( Fig. 5 g and h). Fig. 5 g shows a whole mount of the implant tube position and greater collagen deposition (stained in blue) in the FNPEG+ and to FNPEG++ implanted bones, relative to the FNPEG- control, which did not stain for collagen around the defect. Fig. 5 h shows the formation of new tissue within the implant tube in more detail. Cell infiltration (as denoted by black arrows in Fig. 5 h) was observed in the FNPEG- hydrogels along the defect. The structures seen in this condition appear to resemble fat tissue. Some bone matrix deposits were observed at the outer part of the implant, probably to mechanically support the area. This is supported by the presence of osteoclasts at the proximal end of the defect ( Fig. S8 ), which would increase bone resorption in that area ( Fig. 5 g).
Publisher Copyright:
© 2020 The Authors
PY - 2020/9
Y1 - 2020/9
N2 - Extracellular matrix (ECM)-derived matrices such as Matrigel are used to culture numerous cell types in vitro as they recapitulate ECM properties that support cell growth, organisation, migration and differentiation. These ECM-derived matrices contain various growth factors which make them highly bioactive. However, they suffer lot-to-lot variability, undefined composition and lack of controlled physical properties. There is a need to develop rationally designed biomaterials that can also recapitulate ECM roles. Here, we report the development of fibronectin (FN)-based 3D hydrogels of controlled stiffness and degradability that incorporate full-length FN to enable solid-phase presentation of growth factors in a physiological manner. We demonstrate, in vitro and in vivo, the effect of incorporating vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP2) in these hydrogels to enhance angiogenesis and bone regeneration, respectively. These hydrogels represent a step-change in the design of well-defined, reproducible, synthetic microenvironments for 3D cell culture that incorporate growth factors to achieve functional effects.
AB - Extracellular matrix (ECM)-derived matrices such as Matrigel are used to culture numerous cell types in vitro as they recapitulate ECM properties that support cell growth, organisation, migration and differentiation. These ECM-derived matrices contain various growth factors which make them highly bioactive. However, they suffer lot-to-lot variability, undefined composition and lack of controlled physical properties. There is a need to develop rationally designed biomaterials that can also recapitulate ECM roles. Here, we report the development of fibronectin (FN)-based 3D hydrogels of controlled stiffness and degradability that incorporate full-length FN to enable solid-phase presentation of growth factors in a physiological manner. We demonstrate, in vitro and in vivo, the effect of incorporating vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP2) in these hydrogels to enhance angiogenesis and bone regeneration, respectively. These hydrogels represent a step-change in the design of well-defined, reproducible, synthetic microenvironments for 3D cell culture that incorporate growth factors to achieve functional effects.
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U2 - 10.1016/j.biomaterials.2020.120104
DO - 10.1016/j.biomaterials.2020.120104
M3 - Article
C2 - 32422492
AN - SCOPUS:85084597254
SN - 0142-9612
VL - 252
JO - Biomaterials
JF - Biomaterials
M1 - 120104
ER -